Hydrochloric Acid → HCID 178450972, compound

HRID 2096115Notes

Reaction equation

HRID 2096115 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[C:5]([CH3:23])([CH3:22])[CH2:6][C@H:7]([NH2:21])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].Cl.[OH:26][C:27]1[CH:31]=[C:30]([C:32]([OH:34])=O)[O:29][N:28]=1.[CH3:35][CH2:36]N=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>O1CCOCC1.CN(C=O)C.C(O)CCC>[CH2:1]([O:3][C:4](=[O:24])[C:5]([CH3:23])([CH3:22])[CH2:6][C@H:7]([NH:21][C:32]([C:30]1[O:29][N:28]=[C:27]([OH:26])[CH:31]=1)=[O:34])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:35][CH3:36]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 68180969(R)-4-Amino-5-biphenyl-4-yl-2,2-dimethyl-pentanoic acid ethyl esterHCID 178524642HCID 178524642, compound

Product 1

HCID 178450972HCID 178450972, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

(R)-4-Amino-5-biphenyl-4-yl-2,2-dimethyl-pentanoic acid ethyl ester (72.1 mg, 221 μmol, 1.0 eq.) was combined with dry butyl alcohol (5 mL) and 4N HCl in dioxane (1 mL) and stirred at 60° C. overnight. The solvent where evaporated and azeotroped with toluene. To this was added a mixture of 3-Hydroxyisoxazole-5-carboxylic acid (28.6 mg, 221 μmol, 1.0 eq.), EDCI (39.2 μL, 1.0 eq.) and HOBt (29.9 mg, 221 μmol, 1.0 eq.) that had been combined in DMF (0.2 mL) and stirred for 5 minutes at room temperature. The resulting mixture was stirred for 30 minutes. The reaction was quenched with AcOH and the product was purified by preparative HPLC and lyophilized to yield the title compound (40 mg, 95% purity). MS m/z [M+H]+ calc'd for C27H32N2O5, 465.23; found 465.4.

Workup

  1. customThe solvent where evaporated
  2. customazeotroped with toluene
  3. additionTo this was added
  4. stirringstirred for 5 minutes at room temperature
  5. stirringThe resulting mixture was stirred for 30 minutes
  6. customThe reaction was quenched with AcOH
  7. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-f2f7e58686f74fef88a327188469518c
Source dataset
uspto-grants-2013_05
Patent number
US08449890B2

Reaction notes

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